Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in South African children.

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50 mg Fe as FeSO4 (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time × treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammation.

Effect of purified ß-glucans derived from Laminaria digitata, Laminaria hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations, volatile fatty acids and pro-inflammatory cytokines in the gastrointestinal tract of pigs.

ß-Glucans have been identified as natural biomolecules with immunomodulatory activity. The first objective of the present study was to compare the effects of purified ß-glucans derived from Laminaria digitata, L. hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations and intestinal volatile fatty acid (VFA) production. The second aim was to compare the gene expression profiles of the markers of pro- and anti-inflammation in both unchallenged and lipopolysaccharide (LPS)-challenged ileal and colonic tissues. ß-Glucans were included at 250 mg/kg in the diets. The ß-glucans derived from L. hyperborea, L. digitata and S. cerevisiae all reduced the Enterobacteriaceae population (P<0·05) without influencing the lactobacilli and bifidobacteria populations (P>0·05) in the ileum and colon. There was a significant interaction between gastrointestinal region and ß-glucan source in the expression of cytokine markers, IL-1α (<0·001), IL-10 (P<0·05), TNF-α (P<0·05) and IL-17A (P<0·001). ß-Glucans did not stimulate any pro- or anti-inflammatory cytokine markers in the ileal epithelial cells. In contrast, the expression of a panel of pro- and anti-inflammatory cytokines (IL-1α, IL-10, TNF-α and IL-17A) was down-regulated in the colon following exposure to ß-glucans from all the three sources. However, the data suggest that the soluble ß-glucans derived from L. digitata may be acting via a different mechanism from the insoluble ß-glucans derived from L. hyperborea and S. cerevisiae, as the VFA profile was different in the L. digitata-treated animals. There was an increase in IL-8 gene expression (P<0·05) in the gastrointestinal tract from the animals exposed to L. digitata following an LPS ex vivo challenge that was not evident in the other two treatment groups. In conclusion, ß-glucans from both seaweed and yeast sources reduce Enterobacteriaceae counts and pro-inflammatory markers in the colon, though the mechanisms of action may be different between the soluble and insoluble fibre sources.

Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic disease characterized by the variable clinical picture with the inflammatory changes which can involve the whole colon or its distal part. The current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is a considerable interest in finding alternative and more tolerable treatments for this serious disease. Several lines of experimental studies have shown that melatonin (MEL) regulates the extensive gut immune system and exerts antiinflammatory and immunomodulatory effects suggesting its beneficial action in UC by reducing and controlling inflammation. The study aimed at evaluating the effect of MEL on the activity of inflammatory process and sustaining the remission in patients with UC. It comprised 60 patients with left-sided UC, divided in two equal groups of 30 patients each (38 women and 22 men, aged 26-49 years), similar in both groups, who were in clinical remission for the last 12 months. Patients, during a next period of 12 months, were given mesalazine in daily doses 2 x 1.0 g and melatonin 5 mg daily at bedtime (group I) or placebo (group II). All the patients on MEL adjuvant treatment remained in remission during 12 months of observation with The Mayo Clinic Disease Activity Index (MCDAI) values 1.50±0.51 at the beginning and 2.75±1.86 points after 12 months. In the placebo group significantly higher MCDAI values were observed than in patients on MEL after 6, 9 and 12 months. At the inclusion MCDAI was 1.61±0.68 points and at the end of observation it reached the value of 5.10±2.22 points. In MEL group CRP level remained within the normal range during the course of the study (from 3.49±1.40 to 4.17±2.10 mg/dl). Whereas in the placebo group from the end of the third month the steady rise in CRP blood concentration was noted from 3.85±1.29 to 13.13±6.08 mg/dl. Parallelly to CRP rise a significant decrease in hemoglobin concentration in blood from 12.05±0.69 to 10.93±0.81 g/dl was observed in patients receiving placebo and the values significantly differed between the groups after 3 (p<0.05), 6, 9 and 12 months (p<0.01). The level of anxiety and the intensity of depression in patients on adjuvant MEL decreased during the study but there were no statistical differences noted between the groups. The results of the study allowed drawing the conclusion that adjuvant melatonin therapy may help in sustaining remission in patients with UC.

Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer.

Pioneering work in the 1990s first linked a novel microaerobic bacterium, Helicobacter hepaticus, with chronic active hepatitis and inflammatory bowel disease in several murine models. Targeted H. hepaticus infection experiments subsequently demonstrated its ability to induce colitis, colorectal cancer, and extraintestinal diseases in a number of mouse strains with defects in immune function and/or regulation. H. hepaticus is now widely utilized as a model system to dissect how intestinal microbiota interact with the host to produce both inflammatory and tolerogenic responses. This model has been used to make important advances in understanding factors that regulate both acquired and innate immune response within the intestine. Further, it has been an effective tool to help define the function of regulatory T cells, including their ability to directly inhibit the innate inflammatory response to gut microbiota. The complete genomic sequence of H. hepaticus has advanced the identification of several virulence factors and aided in the elucidation of H. hepaticus pathogenesis. Delineating targets of H. hepaticus virulence factors could facilitate novel approaches to treating microbially induced lower bowel inflammatory diseases.